[Effect of vascular endothelial growth factor antisense oligodeoxynucleotides on angiogenesis in lymphoma of nude mice].

BACKGROUND & OBJECTIVE: It has been reported that vascular endothelial growth factor (VEGF) plays an important role in progression of lymphoma, and lymphoma with high level of VEGF is likely to metastasise at early stage. This study was to explore effects of antisense oligodeoxynucleotides (ASODN) targeting VEGF on angiogenesis of lymphoma through in vitro, and in vivo experiments.

METHODS: Human lymphoma cell line Namalwa cells were incubated with VEGF ASODN (final concentrations were 10, 20, and 30 micromol/L, respectively), or scrambled sequence for 24 h or 48 h. VEGF mRNA expression in treated cells was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), and its protein expression was detected by SP immunohistochemistry. After incubation of 30 micromol/L of VEGF ASODN, 30 micromol/L of scrambled sequence, and PBS as negative control, Namalwa cells were injected into nude mice. Diameters of tumors in ASODN group (6 mice), scrambled sequence group (6 mice), and PBS group (4 mice) were measured, microvessel density (MVD) was detected via immunohistochemistry.

RESULTS: Expression of VEGF mRNA in cells treated with 10, 20, and 30 micromol/L of ASODN were 1.28, 0.86, and 0.47, respectively; those of PBS-treated cells, and scrambled sequence-treated cells were 1.79, and 1.84. Positive rate of VEGF protein in ASODN-treated cells was significantly lower than those in scrambled sequence-treated cells, and PBS-treated cells (23.3% vs. 46.9%, and 47.8%, P<0.05). MVDs of ASODN group, scrambled sequence group, and PBS group were 12.26+/-0.78, 23.92+/-1.14, and 24.13+/-1.21, respectively.

CONCLUSION: VEGF ASODN can down-regulate expression of VEGF, and suppress angiogenesis in lymphoma.